ABSTRACT Tumor-derived circulating exosomes has been emerging in fundamental cancer research, clinical diagnosis and monitoring of treatment responses. However, the specific preparation of enriched, distinct exosome populations is still challenging. Currently, the most common procedure for purifying exosomes involves a series of high-speed ultracentrifugation steps in order to remove cell debris and pellet exosomes. Commercially available exosome isolation kits still need a benchtop centrifuge before the chemical precipitation of exosomal molecular contents. The isolation protocols are tedious and time-consuming (? 10 h) with relatively low yield and recovery purity (? 25%). In order to substantially improve isolation performance and throughput, Clara Diagnostics Inc. proposes to develop a microfluidic-based isolation platform as a research tool for automated, high-specific and high throughput processing of tumor-exosomes and subtypes from a wide variety of biofluids, in response to NIH PA-17-302 SBIR Phase I Funding Opportunity. Currently, there is no any microfluidic-based exosome isolation platform commercially available, although microfluidic technology has proved unmatched capability for exosome processing and molecular profiling. Clara Diagnostics Inc. aims to fulfill this gap by developing the first microdevice product which enables the automated, high-throughput and continuous processing of 96 samples on demand. The implementation of magnetic anisotropic oscillation in 96-channel microfluidic device enables ultra-fast mixing of beads with biofluids while using high flow rates. The single channel processing speed is ~30 ?L/min with a throughput of 96 channels. Note that conventional ultracentrifugation or differential centrifugation processes total blood plasma volume of ~12 mL in 10 h or 6 samples per run. Our proposed platform can process 96 samples with total processing volume of ~1,728 mL in 10 h, which is ~ 144-fold increase. Together with the high-throughput operation and high-specificity to tumor- exosomes and subtypes, we will deliver a generic, enabling platform for preparing enriched, distinct exosome subpopulations from a wide variety of biofluids, such as blood serum, plasma, urine, saliva, cell culture medium, malignant ascites, and milk. This product as a research tool can process sample volumes from 96 channels in microliter for on-chip analysis to milliliter preparation for variable downstream benchtop measurements and therapeutic applications (e.g., mass spectrometry, PCR, and sequencing, and delivery carrier). In strong contrast to current commercial exosome isolation kits, the proposed microfluidic platform will present a new-generation of product that offers unmatched sample processing capabilities for exosome research and immensely accelerates cancer research and clinical development of liquid-biopsy.